Long-term outcomes of combined hepatocellular-cholangiocarcinoma after hepatectomy or liver transplantation: A systematic review and meta-analysis

Background: Combined hepatocellular-cholangiocarcinoma(cHCC-CC) is a rare primary liver malignancy. We conducted a systematic review and meta-analysis to assess the evidence available on the long-term outcomes of cHCC-CC patients after either hepatectomy or liver transplantation(LT). Data Sources: Relevant studies published between January 2000 and January 2018 were identified by searching Pub Med and Embase and reviewed systematically. Data were pooled using a random-effects model. Results: A total of 42 observational studies involving 1691 patients(1390 for partial hepatectomy and 301 for LT) were included in the analysis. The median tumor recurrence and 5-year overall survival(OS) rates were 65%(range 38%–100%) and 29%(range 0–63%) after hepatectomy versus 54%(range 14%–93%) and 41%(range 16%–73%) after LT, respectively. Meta-analysis found no significant difference in OS and tumor recurrence between LT and hepatectomy groups. Conclusion: Hepatectomy rather than LT should be considered as the prior treatment option for cHCC-CC.

Combined liver and kidney transplantation in Guangzhou,China

BACKGROUND: When liver or kidney transplant can respectively cure end-stage liver or kidney disease, neither hepatic graft nor renal transplant alone can be used as a radical therapy for diseases which involve both liver and kidney. Combined liver and kidney transplantation commenced late in China, and the number of transplants has been limited. This study was designed to assess the effects of simultaneous combined liver and kidney transplantation (SLKT) on end-stage liver and kidney diseases. METHODS: Fifteen patients who had received SLKT from 1996 to 2006 in the First Affiliated Hospital of Sun Yat-Sen University were reviewed. They included 5 patients with polycystic liver and kidney, 5 patients with hepatic cirrhosis and renal failure, and 5 patients with fulminant hepatic failure and hepatorenal syndrome (11 men and 4 women; average age 43.5 years). All patients had combined liver and kidney transplantation. RESULTS: The 5 patients with polycystic liver and kidney have survived for more than one year after SLKT, and the longest survival has been 5 years. Three of the 5 patients with hepatic cirrhosis and renal failure have survived more than two years; one died perioperatively and the other died from recurrence of hepatitis B 18 months after the operation. Three of the 5 patients with fulminant hepatic failure and hepatorenal syndrome have survived for two years, and 2 died of multiple organ failure during the operation. CONCLUSIONS: SLKT is an effective therapy for end-stage liver and kidney disease but the indications of SLKT for hepatorenal syndrome should be strict. SLKT may immunologically protect the renal graft.

Combined liver and kidney transplantation in children and long-term outcome

Combined liver-kidney transplantation(CLKT)is a rarely performed complex surgical procedure in children and involves transplantation of kidney and either whole or part of liver donated by the same individual(usually a cadaver)to the same recipient during a single surgical procedure.Most common indications for CLKT in children are autosomal recessive polycystic kidney disease and primary hyperoxaluria type 1.Atypical haemolytic uremic syndrome,methylmalonic academia,and conditions where liver and renal failure co-exists may be indications for CLKT.CLKT is often preferred over sequential liver-kidney transplantation due to immunoprotective effects of transplanted liver on renal allograft;however,liver survival has no significant impact.Since CLKT is a major surgical procedure which involves multiple and complex anastomosis surgeries,acute complications are not uncommon.Bleeding,thrombosis,haemodynamic instability,infections,acute cellular rejections,renal and liver dysfunction are acute complications.The long-term outlook is promising with over 80%5-year survival rates among those children who survive the initial six-month postoperative period.

Non-composite combined liver and intestinal allotransplantation

BACKGROUND: Patients with short bowel syndrome may require combined liver and intestinal transplantation due to total parenteral nutrition(TPN)-related liver damage. We report combined liver and intestinal allotransplantation as a non-composite technique in a patient in China. METHODS: During the operation, a 380 cm long intestine was transplanted with systemic drainage and aortic inflow, while the liver graft was placed in a piggyback fashion. Warm ischemic time of the donor graft was 2 minutes and 30 seconds, and cold ischemic time for intestinal and the liver graft was 6 hours and 40 minutes and 8 hours and 7 minutes, respectively. Immunosuppressants used after operation included tacrolimus, methylprednisolone, mycophenolate mofetil and Zenapax. RESULTS: The recipient recovered with no evidence of rejection and was kept well on tube feeding. Eventually, he died of massive hemorrhage of the thoracic cavity on day 210 after transplantation. CONCLUSION: The non-composite combined liver and intestinal allotransplantation is superior to composite technique in adult patients, particularly those who have had abdominal infection or repeated abdominal operations.

EFFECTS OF BLOOD TRANSFUSION ON BONE MARROW TRANSPLANTATION IN RATS WITH RADIATION-BURN COMBINED INJURY

The effects of pre-irradiation blood transfusion(BT)on survival rateof radiation-burn combinedly injured rats receiving bone marrow transplantation(BMT) were studied. It was found that after 9-11 Gy of radiation was given, the 90-daysurvival rate of the rats receiving BT(72%) and BMT was significantly higher than thatof those receiving BMT only(42%)(P<0.01).In those rats surviving over 100 days,cells of donor type could be found. In the first 30 days of surviving, the number of Tcells was significantly higher in the BMT alone group than in the group of BMT plusBT, but no difference In restoration of B cell was revealed. The findings suggest that BTcould promote the recipient's tolerance to BMT. The effects of BT on BMT are similarto those on skin grafting.

T CELL REPERTOIRE COMPLEXITY IN SEVER COMBINED IMMUNODEFICIENCY PATIENTS AFTER BONE MARROW TRANSPLANTATION

Objective. To study thymus-dependent T cell development and T cell repertoire in human s ever com-bined immunodeficiencypatients after HLA-identical or haploid entical T cell-depleted allogeneic bone marrow transplantation.Methods .Blood samples were obtained from15SCID patients before transplantation and a t varying intervals thereafter.Quantitative competitive PCR assay and immunosco pe analysis of the T cell receptorVarepertoire were performed.Results. Before and within the first100days after transplantation,patients’ periphera l blood mononuclear cellpresented an oligoclonal or polyclonal skewed T cell repertoire,low T cell re-ceptor excision circlesvalues and pred ominance of CD45RO + T cell.In contrast,the presence of high numbers of CD45RA + T cells in bone marrowcirculation reconstituted SCID patients(>10 0days post-transplantation)correlated with active T cell production by the th ymus as revealed by high TREC values,and a polyclonal T cell repertoire demonst rated by a Gaussian distribution of Va-specific peaks.Conclusions.Within one year after BMT ,a normal T cell repertoire develops in SCID patients as a resu lt of thymic output.The T cell receptor diversity is highly and positively corr elated in these patients with TREC levels.

Combined liver-kidney transplantation for rare diseases

Combined liver and kidney transplantation(CLKT)is indicated in patients with failure of both organs,or for the treatment of end-stage chronic kidney disease(ESKD)caused by a genetic defect in the liver.The aim of the present review is to provide the most up-to-date overview of the rare conditions as indications for CLKT.They are major indications for CLKT in children.However,in some of them(e.g.,atypical hemolytic uremic syndrome or primary hyperoxaluria),CLKT may be required in adults as well.Primary hyperoxaluria is divided into three types,of which type 1 and 2 lead to ESKD.CLKT has been proven effective in renal function replacement,at the same time preventing recurrence of the disease.Nephronophthisis is associated with liver fibrosis in 5%of cases and these patients are candidates for CLKT.In alpha 1-antitrypsin deficiency,hereditary C3 deficiency,lecithin cholesterol acyltransferase deficiency and glycogen storage diseases,glomerular or tubulointerstitial disease can lead to chronic kidney disease.Liver transplantation as a part of CLKT corrects underlying genetic and consequent metabolic abnormality.In atypical hemolytic uremic syndrome caused by mutations in the genes for factor H,successful CLKT has been reported in a small number of patients.However,for this indication,CLKT has been largely replaced by eculizumab,an anti-C5 antibody.CLKT has been well established to provide immune protection of the transplanted kidney against donor-specific antibodies against class I HLA,facilitating transplantation in a highly sensitized recipient.

A comparative study of pancreatic endocrine function and related metabolism after long-term survival between the patients with combined kidneypancreas transplantation vs those with combined en bloc ' liver-pancreas transplantation

Objective To compare the effects of combined en bloc liver - pancreas transplantation ( LPT) with portal vein drainage and simultaneous combined kidney - pancreas transplantation ( KPT) with systemic venous drainage on the pancreatic endocrine function and related me-

A single center experience of combined liver and kidney transplantation

Objective To summarize the experience of treating the end stage of liver disease complicated with renal failure using combined liver - kidney transplantation. Methods The clinical data of 28 cases receiving combined liver - kidney transplantation were retrospectively ana-

THE MUTUAL BENEFIT ROLE OF LIVER AND PANCREAS IN COMBINED TRANSPLANTATION

The present study observed the mutual benefit role of liver and pancreas in combined hepaticopan-creatic transplantation in rats. The results indicated that pancreas, when transplanted with liver, could survive for a significant long time (13. 4±1.01 days) than it transplanted alone (9. 2±1.14 days) (P< 0. 05, t test). The interstitial rejection was mild and its rejection grade was significantly different from that of pancreas transplanted alone (P<0. 05, X2 test). The liver, when transplanted with pancreas, regenerated with strong competence and contact structure morphologically compared with liver transplanted alone. We think that pancreas could be immunologically protected against rejection and liver can be nutri-tionalized by pancreas in combined liver and pancreas transplantation.

COMBINATION OF ACUPUNCTURE ANALGESIA AND EPIDURAL BLOCK IN RENAL TRANSPLANTATION

One hundred patients undergoing renal transplantation were randomly divided into com-bined acupuncture-epidural anesthesia group (group A, points selected: Ciliao, Sanyinjiao, Taixi to-gether with Shenyu and para-incision or Zusanli; combined with small dose of epidural block) and epidural block group (group C), each 50 patients. The initial dose and total dose of local anesthetics were 5. 6 ±0. 3 ml and 13. 5±1.0ml in group A, and 14. 5±0. 4 ml and 25. 4 ±1. 2 ml in group C,respectively. There was very significant difference between the two groups (P< 0.001 ). During the operation the hemodynaminc changes were greater in group C. Ephedrine and atropine were used in 1 and 2 cases in group A, and in 9 and 5 cases in group C, respectively. The starting time of urination of the transplanted kidney was shorter in group A than in group C, being 209±25 s and 410±47 s, re-spectively (P<0.001 ). There was no significant difference in the indices of immmunologic function between the two groups. The anesthetic results in group A were evaluated according to the initial dose of epidural anesthetics. Those were excellent in 31 cases (62 % ) and good in 13 (26% ) with the ex-cellent-good rate 88 %.

Dual-targeted treatment for inflammatory bowel disease:Whether fecal microbiota transplantation can be an important part of it

Inflammatory bowel disease(IBD)is a chronic gastrointestinal inflammatory disease.With the emergence of biologics and other therapeutic methods,two biologics or one biologic combined with a novel small-molecule drug has been proposed in recent years to treat IBD.Although treatment strategies for IBD are being optimized,their efficacy and risks still warrant further consideration.This editorial explores the current risks associated with dual-targeted treatment for IBD and the great potential that fecal microbiota transplantation(FMT)may have for use in combination therapy for IBD.We are focused on addressing refractory IBD or biologically resistant IBD based on currently available dual-targeted treatment by incorporating FMT as part of this dual-targeted treatment.In this new therapy regimen,FMT represents a promising combination therapy.

Asia's first combined liver transplant and aortic valve replacement

To the editor:Liver transplantation is the only cure for patients with endstage liver disease.It is however an ultra-major surgery which is physiologically challenging to the cardiopulmonary function of the patients.Hence,in patients who also have valvular heart disease or coronary artery disease,liver transplantation would be con-

Combined use of retroperitoneal laparoscopy and bladder resectoscope to treat renal and ureteral tumor occurring at the same side of transplanted kidney (report of 5 cases)

To evaluate the operative characteristics and efficacy of retroperitoneoscopic resection of renal,ureter and partial bladder for the treatment of native renal pelvic and ureteral transitional cell cancer occurring at the same side of transplanted kidney.Methods In 5 cases of renal transplantation,there were 2 cases of right native renal pelvic cancer,1 case of right native renal pelvic and ureter cancer and 2 cases of right ureter cancer respectively.The transplanted kidney was in the same iliac fossa side of the tumor.All 5 patients were subjected to nephroureterectomy and bladder cuff excision by retroperitoneoscopic technique.Results Five operations were completed successfully.The operative time was 180 to 280 min,and the blood loss was 50 to 200 ml.The recovery of intestinal function after operation was 12 to 36 h.The urine output was 1 500 to 4 000 per day.Postoperative serum creatinine was still normal.The mean hospital stay after operation was 4.5 days.Conclusion Retroperitoneal laparoscopic nephroureterectomy and bladder cuff excision is a good method to treat the native renal pelvic and ureteral transitional cell cancer occurring at the same side of transplanted kidney.The procedure is safe and less invasive,which provides a good protection of transplanted kidney.12 refs.

Design and Experimental Research on Seedling Pick-Up Mechanism of Planetary Gear Train with Combined Non-circular Gear Transmission

Currently, transplanting mechanisms for dryland plug seedlings in China are mainly semiautomatic and have low efficiency. The rotary seedling pick-up mechanism with a planetary gear train for non-uniform intermittent transmission, and a concave and convex locking arc device, has a large rigid impact. To solve these problems, according to the design requirements for a dryland plug seedling transplanting mechanism, a rotary seedling pick-up mechanism of a planetary gear train with combined non-circular gear transmission of incomplete eccentric circular and noncircular gears was proposed. This has the characteristics of two-times greater fluctuation of the transmission ratio in a cycle, and can achieve a non-uniform continuous drive. Through analysis of the working principle of the seedling pick-up mechanism, its kinematics model was established. The human–computer interaction optimization method and self-developed computer-aided analysis and optimization software were used to obtain a set of parameters that satisfy the operation requirements of the seedling pick-up mechanism. According to the optimized parameters, the structure of the seedling pick-up mechanism was designed, a virtual prototype of the mechanism was created, and a physical prototype was manufactured. A virtual motion simulation of the mechanism was performed, high-speed photographic kinematics tests were conducted, and the kinematic properties of the physical prototype were investigated, whereby the correctness of the theoretical model and the optimized design of the mechanism were verified. Further, laboratory seedling pick-up tests were conducted. The success ratio of seedling pick-up was 93.8% when the seedling pick-up efficiency of the mechanism was 60 plants per minute per row, indicating that the mechanism has a high efficiency and success ratio for seedling pick-up and can be applied to a dryland plug seedling transplanter.

Orthotopic liver transplantation in treatment of 77patients with end-stage hepatic disease

Objective: To summarize the experience of human or-thotopic liver transplantation(OLTx) in treatment ofpatients with end-stage hepatic disease and their peri-operative management.Methods: A retrospective analysis was made on OLTxperformed in 77 patients from April 1993 to September2001 in our department included combined liver-kid-ney transplantation (6 patients) and living related livertransplantation (2). Among them, 76 were adults and1 was infant (67 males and 10 females) . The donors in-cluded 7S non-heart beating donors and 2 living re-lated donors. Veno-venous bypass was used only in 45cases during the operation. Immunosuppressive agentsconsisted of cyclosporine, cellcept, ALG corticosteroidsand FK506.Results: The one-year survival rates of grafts and re-cipients with benign hepatic disease were 75%. Therecipients this year are surviving with good function ofgrafts.Conclusion: Liver transplantation is the best therapeu-tic method for a large number of patients with end-stage hepatic disease in China.

Conversion therapy in liver transplantation for hepatocellular carcinoma:What's new in the era of molecular and immune therapy?

Background:Hepatocellular carcinoma(HCC)is the sixth most common cancer globally,with limited therapies and unsatisfactory prognosis once in the advanced stages.With promising advances in locoregional and systematic treatments,fast development of targeted drugs,the success of immunotherapy,as well as the emergence of the therapeutic alliance,conversion therapy has recently become more well developed and an effective therapeutic strategy.This article aimed to review recent developments in conversion therapy in liver transplantation(LT)for HCC.Data sources:We searched for relevant publications on Pub Med before September 2022,using the terms“HCC”,“liver transplantation”,“downstaging”,“bridging treatment”and“conversion therapy.”Results:Conversion therapy was frequently represented as a combination of multiple treatment modalities to downstage HCC and make patients eligible for LT.Although combining various local and systematic treatments in conversion therapy is still controversial,growing evidence has suggested that multimodal combined treatment strategies downstage HCC in a shorter time,which ultimately increases the opportunities for LT.Moreover,the recent breakthrough of immunotherapy and targeted therapy for HCC also benefit patients with advanced-stage tumors.Conclusions:In the era of targeted therapy and immunotherapy,applying the thinking of transplant oncology to benefit HCC patients receiving LT is a new topic that has shed light on advanced-stage patients.With the expansion of conversion therapy concepts,further investigation and research is required to realize the full potential of conversion treatment strategies,including accurately selecting candidates,determining the timing of surgery,improving the conversion rate,and guaranteeing the safety and long-term efficacy of treatment.

Initial steroid-free immunosuppression after liver transplantation in recipients with hepatitis c virus related cirrhosis

AIM:Steroids can increase hepatitis C virus(HCV) replication.After liver transplantation(LTx),steroids are commonly used for immunosuppression and acute rejection is usually treated by high steroid dosages.Steroids can worsen the outcome of recurrent HCV infection.Therefore, we evaluated the outcome of HCV infected liver recipients receiving initial steroid-free immunosuppression. METHODS:Thirty patients undergoing LTx received initial steroid-free immunosuppression.Indication for LTx included 7 patients with HCV related cirrhosis.Initial immunosuppression consisted of tacrolimus 2×0.05mg/kg.d po and mycophenolate mofetil(MMF)2×15mg/kg.d po.The tacrolimus dosage was adjusted to trough levels in the target range of 10-15μg/L during the first 3 mo and 5-10μg/L thereafter.Manifestations of acute rejection were verified histologically. RESULTS:Patient and graft survival of 30 patients receiving initial steroid-free immunosuppression was 86% and 83% at 1 and 2 years.Acute rejection occurred in 8/30 patients, including 1 HCV infected recipient.All HCV-infected patients had HCV genotype Ⅱ(lb).HCV seropositivity occurred within the first 4 mo after LTx.The virus load was not remarkably increased during the first year after LTx.Histologically,grafts had no severe recurrent hepatitis. CONCLUSION:From our experience,initial steroid-free immunosuppression does not increase the risk of acute rejection in HCV infected liver recipients.Furthermore,none of the HCV infected patients developed serious chronic liver diseases.It suggests that it may be beneficial to avoid steroids in this particular group of patients after LTx.

Enzymes activity of intestinal grafts after liver small bowel transplantation in rats

OBJECTIVES: To investigate the activity alterations of enzymes in intestine grafts after liver/small bowel transplantation in rats and the relations of these changes to immune rejection of grafts. METHODS: A model of liver/small bowel transplantation (LSBT) was established in closed colony SD and Wistar rats. The activity of enzymes including triphosphatase (ATPase), alkalinophosphatase (AKP), acytelcholinesterase (AchE), oxidesynthase (NOS) and monoamine oxidase (MAO) in bowel grafts was studied histochemically at regular postoperative intervals. RESULTS: The activity of enzymes in the wall of the grafts disappeared eventually in isolated small bowel transplantation (SBT) rats. In contrast, the activity in LSBT rats remained and recovered postoperatively. CONCLUSIONS: The rejection in grafted intestine could be prevented or delayed in LSBT rats. The changes in the activity of enzymes and neurons might be used to detect the rejection and function of the graft.

Factors associated with 5-year survival of combined hepatocellular and cholangiocarcinoma

BACKGROUND Combined hepatocellular and cholangiocarcinoma(HCC/CC)is a rare primary hepatic malignancy which carries a poor prognosis due to its aggressive nature.Few centers have enough cases to draw definitive conclusions and there is limited understanding of prognosis.Given the rarity of HCC/CC,an analysis of large national cancer database was needed to obtain larger number of HCC/CC cases.AIM To identify associated factors for 5-year survival of HCC/CC.METHODS We conducted a retrospective study of The Surveillance,Epidemiology,and End Results(SEER)database obtained from SEER*Stat 8.3.6 software.Previously defined histology code 8180 for the International Classification of Disease for Oncology,3rd edition was used to identify HCC/CC cases from 2004 to 2015.We collected demographics,American Joint Committee on Cancer(AJCC)stage,treatment,tumor size,and survival data.These data were converted to categorical variables.The Shapiro-Wilk normality test was used to assess normal distribution.Mann-Whitney U test was used to compare continuous variables without normal distribution,and t-test was used to compare continuous variables with a normal distribution.The Kaplan-Meier survival curve analyzed 5-year survival.Univariate and multivariate logistic regression model was used to analyze factors associated with 5-year survival.Multivariate Cox proportional hazard regression was done on 5-year survival.We defined P<0.05 was statistically significant.RESULTS We identified 497 patients with the following characteristics:Mean age 62.4 years(SD:11.3),149(30.0%)were female,racial distribution was:276(55.5%)white,53(10.7%)black,84(16.9%)Asian and Pacific Islander(API),77(15.5%)Hispanic,and 7(1.4%)others or unknown.Stage I/II disease occurred in 41.5%and tumor size<50 mm was seen in 35.6%of patients.Twenty-four(4.8%)received locoregional therapy(LRT),119(23.9%)underwent resection,and 50(10.1%)underwent liver transplantation.The overall median survival was 6 mo[Interquartile range(IQR):1-22].After multivariate logistic regression,tumor size<50 mm[Odds ratios(OR):2.415,P=0.05],resection(OR:12.849,P<0.01),and transplant(OR:27.129,P<0.01)showed significance for 5-year survival.Age>60,sex,race,AJCC stages,metastasis,and LRT were not significant.However,API vs white showed significant OR of 2.793(CI:1.120-6.967).Cox proportional hazard regression showed AJCC stages,tumor size<50 mm,LRT,resection,and transplant showed significant hazard ratio.CONCLUSION HCC/CC patients with tumor size<50 mm,resection,and transplant were associated with an increase in 5-year survival.API showed advantageous OR and hazard ratios over white,black.